Abstract

There is growing recognition that the risk of attention-deficit hyperactivity disorder (ADHD) in children may be influenced by micronutrient deficiencies, including iron. We conducted this meta-analysis to examine the association between ADHD and iron levels/iron deficiency (ID). We searched for the databases of the PubMed, ScienceDirect, Cochrane CENTRAL, and ClinicalTrials.gov up to August 9th, 2017. Primary outcomes were differences in peripheral iron levels in children with ADHD versus healthy controls (HCs) and the severity of ADHD symptoms in children with/without ID (Hedges' g) and the pooled adjusted odds ratio (OR) of the association between ADHD and ID. Overall, seventeen articles met the inclusion criteria. Peripheral serum ferritin levels were significantly lower in ADHD children (children with ADHD = 1560, HCs = 4691, Hedges' g = -0.246, p = 0.013), but no significant difference in serum iron or transferrin levels. In addition, the severity of ADHD was significantly higher in the children with ID than those without ID (with ID = 79, without ID = 76, Hedges' g = 0.888, p = 0.002), and there was a significant association between ADHD and ID (OR = 1.636, p = 0.031). Our results suggest that ADHD is associated with lower serum ferritin levels and ID. Future longitudinal studies are required to confirm these associations and to elucidate potential mechanisms.

Forest plots showing effect sizes (Hedges’ g) and 95% confidence intervals (CIs) from individual studies and pooled results of all included studies comparing (A) serum ferritin, (B) serum iron, and (C) serum transferrin levels in children with and without ADHD; (D) Forest plot showing effect sizes (Hedges’ g) and 95% CIs from individual studies and pooled results comparing the severity of ADHD symptoms in children with and without iron deficiency (ID); (E) Forest plot pooling the adjusted odds ratio (OR) comparing the association between ADHD and ID. Figure 2(A) serum ferritin levels (p = 0.013) but not (B) serum iron (p = 0.569) or (C) serum transferrin (p = 0.096) levels were significantly lower in the children with ADHD compared to those without ADHD. Figure 2(D) The severity of ADHD symptoms was significantly greater in the children with ID than in those without ID (p < 0.001). Figure 2(E) indicated a significantly high association between ADHD and ID based on the pooled adjusted OR (p = 0.031).